The proposed research utilizes a model of impaired neurodevelopment in the ferret that presents as a thin and disrupted cerebral cortex, with ectopic clusters of cells typical of cortical dysplasia. During generation of the earliest born neocortical layers, treatment with the antimitotic agent, methylazoxy methanol (MAM), disrupts radial glia, and results in abnormally situated Cajal Retzius cells. Features of the brain resulting from this treatment are an excellent model for study of migration defects. The current proposal investigates the following questions resulting from this model. (1) What causes the radial glia to become disorganized? (2) What prevents cells from migrating effectively into the neocortex? (3) What causes the Cajal Retzius cells to become disorganized? The hypothesis is that a radialization factor is present in normal cortex, and when it is provided to MAM-treated cortex, normal radial glial morphology can be restored. A second, related hypothesis is that the restoration of normal radial glial morphology can improve migration in MAM-treated cortex. These hypotheses will be tested and the biochemical nature of the radialization factor will be defined using organotypic and cell cultures and migration bioassays to analyze this system.